Functional organization and connectivity of the dorsal column nuclei complex reveals a sensorimotor integration and distribution hub

Abstract

The dorsal column nuclei complex (DCN-complex) includes the dorsal column nuclei (DCN, referring to the gracile and cuneate nuclei collectively), external cuneate, X, and Z nuclei, and the median accessory nucleus. The DCN are organized by both somatotopy and modality, and have a diverse range of afferent inputs and projection targets. The functional organization and connectivity of the DCN implicate them in a variety of sensorimotor functions, beyond their commonly accepted role in processing and transmitting somatosensory information to the thalamus, yet this is largely underappreciated in the literature. To consolidate insights into their sensorimotor functions, this review examines the morphology, organization, and connectivity of the DCN and their associated nuclei. First, we briefly discuss the receptors, afferent fibers, and pathways involved in conveying tactile and proprioceptive information to the DCN. Next, we review the modality and somatotopic arrangements of the remaining constituents of the DCN-complex. Finally, we examine and discuss the functional implications of the myriad of DCN-complex projection targets throughout the diencephalon, midbrain, and hindbrain, in addition to their modulatory inputs from the cortex. The organization and connectivity of the DCN-complex suggest that these nuclei should be considered a complex integration and distribution hub for sensorimotor information.

Circuit organization of the excitatory sensorimotor loop through hand/forelimb S1 and M1

“…The PRV labeling using L5A neurons in hand S1 as starter neurons labeled the PO, but also did not lead to additional labeling in the cuneate. Thus, for the hand-related pathways, and in contrast to cuneo-PO projections described in other species such as the cat (Berkley et al, 1986; Loutit et al, 2020), we did not identify a clear cuneo-PO counterpart to the trigemino-PO circuit in the whisker-related paralemniscal pathway. Although ascending subcortical sources of input to hand-related PO neurons in the mouse remain to be identified, descending cortical axons from hand S1 target a subregion of PO, strongly exciting recurrently projecting PO neurons there to form cortico-thalamo-cortical loops (Guo et al, 2020).…”

“…Perhaps the dense incorporation into of multiple types of IT neurons into this 474 circuit increases its computational power by providing an expanded array of targets by which local 475 and long-range inputs from diverse sources can modulate excitatory feedforward excitation along 476 the connections feeding into M1 corticospinal neurons. Whereas this study focused on lemnisco-477 cortical pathways, which chiefly mediate forelimb tactile processing, an important related area for 478 future research is the circuit organization of cuneo-cerebello-cortical pathways, which mediate 479 forelimb proprioceptive processing and are also integrated and modulated at the cortical level 480 (Jorntell and Ekerot, 1999;Loutit et al, 2020;Reschechtko and Pruszynski, 2020). With the many tools now available in mice for in vivo monitoring and modulation of specific cell types, the 482 challenge will be to prioritize which cells and circuits to investigate in which behavioral paradigms.…”

Dorsal Column Nuclei Neural Signal Features Permit Robust Machine-Learning of Natural Tactile- and Proprioception-Dominated Stimuli

“…Some of the hindlimb errors resulted from confusing tactile-and proprioceptive-dominated stimuli of the same limb ( Figures 4A-D, 5B,E). Most hindlimb proprioceptive afferents either project onto DCN neurons in the ventral gracile nuclei or to nuclei X and Z, which are rostral nuclei that form part of the DCN-complex (for a comprehensive review see Loutit et al, 2020). Although both hindlimbs tactile and proprioceptive afferents project to the DCN, the proprioceptive DCN regions may be too deep to acquire HF features, while nuclei X and Z were not covered by the placement of our electrode array.…”

“…Thus, prediction of hindlimb stimuli may have relied mostly on tactile information to discriminate between the tactile and proprioceptive-dominated stimuli and were confined to midline electrodes, thereby reducing overall lower hindlimb prediction accuracy. Meanwhile, the external cuneate nuclei, part of the DCN-complex that exclusively receives forelimb proprioceptive afferents (Loutit et al, 2020), were located partially under the lateral electrodes. Thus, tactile evoked forelimb activity was mainly acquired from both lateral and midline electrodes, whereas proprioceptive evoked forelimb activity was acquired mainly from lateral electrodes.…”

“…Several groups have stimulated monkey or human somatosensory cortex to evoke percepts such as vibration, pressure, and stimulus location, and have shown that this somatosensory feedback improves dexterous manipulation capabilities of motor neural prostheses (O'Doherty et al, 2009(O'Doherty et al, , 2019Tabot et al, 2013;Klaes et al, 2014;Kim et al, 2015;Flesher et al, 2016Flesher et al, , 2019Salas et al, 2018). However, we have recently suggested that the dorsal column nuclei (DCN) and their associated external cuneate nuclei, nuclei X, and Z (DCN-complex) have anatomical advantages over the cortex as a sensory neural prosthesis target (Loutit and Potas, 2020a;Loutit et al, 2020). Activating the DCN-complex with a neural prosthesis capable of mimicking natural somatosensory signals has the potential to simultaneously inform not only the cortex but several other regions essential for motor control, including the cerebellum and tegmentum that are bypassed by a cortical neural prosthesis.…”